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Exercise Capacity and Quality of Life in Patients With PPH Receiving Short Term Oral L-Citrulline Malate

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified September 2012 by Masih Daneshvari Hospital.
Recruitment status was:  Recruiting
Information provided by (Responsible Party):
babak sharif kashani, Masih Daneshvari Hospital Identifier:
First received: September 1, 2012
Last updated: August 8, 2013
Last verified: September 2012
Due to vasodilatory properties of the NO, one of the therapeutic approaches for IPAH is oral use of nitric oxide precursors (10). Efficacy of L-arginine is well-documented in the current literature but there is paucity of data with regard to L-citrulline- malate. Hence, this study will evaluate therapeutic efficacy of L-citrulline- malate in two categories of patients with pulmonary hypertension (IPAH, and Eisenmeger syndrome). This randomized clinical trial utilizes 6-minute walk, pro BNP levels and the echocardiographic indexes an indicator of functional improvement of the patients.

Condition Intervention Phase
Idiopathic Pulmonary Arterial Hypertension
Eisenmenger Syndrome
Drug: L-Citrulline Malate
Early Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Exercise Capacity and Quality of Life in Patients With Idiopathic Pulmonary Hypertension and Eisenmenger Syndrome Receiving Short Term Oral L-Citrulline Malate

Resource links provided by NLM:

Further study details as provided by Masih Daneshvari Hospital:

Primary Outcome Measures:
  • the change in exercise capacity [ Time Frame: 2 weeks ]
    The primary measure of efficacy was the change in exercise capacity, as measured by the total distance walked in six minutes, from baseline to week 2. (15)

Secondary Outcome Measures:
  • changes in mean pulmonary-artery pressure [ Time Frame: 2 weeks ]
    changes in mean pulmonary-artery pressure from baseline to week 2.

Other Outcome Measures:
  • change in the quality of life [ Time Frame: 2 weeks ]
    change in the quality of life from baseline to week 2

Estimated Enrollment: 25
Study Start Date: August 2012
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: L-Citrulline, Exercise Capacity
L-Citrulline malate, 1gr, oral, divided 3 times a day,for 2 weeks
Drug: L-Citrulline Malate
3 gr per day, oral, for 2 weeks
Other Name: Stimol

Detailed Description:

Pulmonary vascular tone is maintained by the action of vasoprotective compounds including nitric oxide (NO)(1).NO can be synthesized endogenously in the body via L-arginine and NOS-independent mechanism from the anion nitrite (NO2-)(2,3).Nitric oxide (NO) causes cyclic guanosine monophosphate-mediated vasodilatation of the pulmonary vasculature. Endogenous NO is also produced from the metabolism of citrulline; an amino acid generated by the urea cycle (4). NO is critical for normal development of the pulmonary vasculature and loss of this vasodilator factor and subsequent endothelial dysfunction is proposed as one of the possible explanations for development of pulmonary hypertension (1).

From a clinical standpoint, pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD).Its presence is associated with shorter survival and worse clinical outcome. In a setting of COPD, pulmonary hypertension tends to be of moderate severity and progresses slowly. Recent investigations have demonstrated endothelial dysfunction and changes in the expression of endothelial-derived mediators that regulate vascular tone and cell growth in the pulmonary arteries of patients with mild disease(5). Pulmonary vascular involvement from congenital heart disease like Eisenmeger syndrome is another important category of patients with PAH. In this congenital disease pulmonary vascular involvement follows a period in which pulmonary resistance is low and pulmonary blood flow is high (6, 7, 8). Finally, Idiopathic pulmonary hypertension (IPAH) is the third category of these patients. IPAH has unknown etiology and is characterized by progressive obliteration of small and medium size pulmonary arteries; elevation in pulmonary arterial pressure, and an increase in pulmonary vascular resistance. Presence of these pathologies eventually leads to right heart failure and death (9).


Ages Eligible for Study:   15 Years to 70 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • all patients less than 70 years old,
  • patients with a six-minute walking distance of more than 100 meters (m),
  • a mean pulmonary arterial pressure (PAP) ≥ 25 mmHg at rest as assessed by right heart catheterization(RHC) (11,12).

Exclusion Criteria:

  • all patients more than 70 years old,
  • patients with a six-minute walking distance of less than 100 meters (m), active pulmonary or extra pulmonary infection,
  • serious coronaropathy and/ or ventricular dysfunction,
  • significant renal illness and/or hepatitis,
  • detected immunosuppressive illnesses,
  • carrier of known neoplasias,
  • pregnancy,
  • lack of family support,
  • psychosocial problems,
  • drug or alcohol abuse, and
  • noncompliance with established medical protocol.
  Contacts and Locations
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Please refer to this study by its identifier: NCT01683981

Contact: babak sharif kashani, Cardiologist 0098-02188883114
Contact: paritash tahmasebpour, MD 0098-09125037861

Iran, Islamic Republic of
MasihDH Recruiting
Tehran, Iran, Islamic Republic of, 021
Contact: babak sharif kashani, cardiologist    0098-02188883114   
Contact: paritash tahmasebpour, MD    0098-09125037861   
Principal Investigator: babak sharif kashani, cardiologist         
Sponsors and Collaborators
Masih Daneshvari Hospital
Principal Investigator: babak sharif kashani, cardiologist Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Science, Tehran, Iran.
Principal Investigator: Paritash Tahmaseb pour, MD MD
  More Information

Responsible Party: babak sharif kashani, Head of Cardiology Department of NRITLD, Associate Professor, Masih Daneshvari Hospital Identifier: NCT01683981     History of Changes
Other Study ID Numbers: f-91-138
Study First Received: September 1, 2012
Last Updated: August 8, 2013

Keywords provided by Masih Daneshvari Hospital:
Idiopathic Pulmonary Arterial Hypertension
Eisenmenger Syndrome
Exercise Capacity
Quality of Life

Additional relevant MeSH terms:
Familial Primary Pulmonary Hypertension
Eisenmenger Complex
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Heart Diseases
Congenital Abnormalities processed this record on April 25, 2017